External baroreflex activation

ABSTRACT

Methods and systems for external baroreflex activation allow a physician to characterize a patient&#39;s response to baroreflex activation prior to providing baroreflex activation therapy. Methods generally include applying a baroreflex activation stimulus to a patient, measuring one or more physiological parameters of the patient, and determining the extent to which the baroreflex activation causes a baroreflex response. Multiple stimuli of different intensities and/or from different locations may be compared. Systems include one or more external baroreflex activation devices and one or more physiological parameter measuring devices. Optionally, a system may also include one or more fully or partially implantable devices for providing baroreflex activation therapy.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 60/549,760, filed Mar. 2, 2004, the full disclosure of which ishereby incorporated by reference.

BACKGROUND OF THE INVENTION

The present invention generally relates to medical devices and methodsfor baroreflex activation. Specifically, the present invention relatesto devices and methods for externally activating the baroreflex systembefore implanting a baroreflex activation device.

Cardiovascular disease is a major contributor to patient illness andmortality. It also is a primary driver of health care expenditure,costing more than $326 billion each year in the United States.Hypertension, or high blood pressure, is a major cardiovascular disorderthat is estimated to affect over 50 million people in the United Satesalone. Of those with hypertension, it is reported that fewer than 30%have their blood pressure under control. Hypertension is a leading causeof heart failure and stroke. It is the primary cause of death in over42,000 patients per year and is listed as a primary or contributingcause of death in over 200,000 patients per year in the U.S.Accordingly, hypertension is a serious health problem demandingsignificant research and development for the treatment thereof.

Hypertension occurs when the body's smaller blood vessels (arterioles)constrict, causing an increase in blood pressure. Because the bloodvessels constrict, the heart must work harder to maintain blood flow atthe higher pressures. Although the body may tolerate short periods ofincreased blood pressure, sustained hypertension may eventually resultin damage to multiple body organs, including the kidneys, brain, eyesand other tissues, causing a variety of maladies associated therewith.The elevated blood pressure may also damage the lining of the bloodvessels, accelerating the process of atherosclerosis and increasing thelikelihood that a blood clot may develop. This could lead to a heartattack and/or stroke. Sustained high blood pressure may eventuallyresult in an enlarged and damaged heart (hypertrophy), which may lead toheart failure.

Heart failure is the final common expression of a variety ofcardiovascular disorders, including ischemic heart disease. It ischaracterized by an inability of the heart to pump enough blood to meetthe body's needs and results in fatigue, reduced exercise capacity andpoor survival. It is estimated that approximately 5,000,000 people inthe United States suffer from heart failure, directly leading to 39,000deaths per year and contributing to another 225,000 deaths per year. Itis also estimated that greater than 400,000 new cases of heart failureare diagnosed each year. Heart failure accounts for over 900,000hospital admissions annually, and is the most common discharge diagnosisin patients over the age of 65 years. It has been reported that the costof treating heart failure in the United States exceeds $20 billionannually. Accordingly, heart failure is also a serious health problemdemanding significant research and development for the treatment and/ormanagement thereof.

Heart failure results in the activation of a number of body systems tocompensate for the heart's inability to pump sufficient blood. Many ofthese responses are mediated by an increase in the level of activationof the sympathetic nervous system, as well as by activation of multipleother neurohormonal responses. Generally speaking, this sympatheticnervous system activation signals the heart to increase heart rate andforce of contraction to increase the cardiac output; it signals thekidneys to expand the blood volume by retaining sodium and water; and itsignals the arterioles to constrict to elevate the blood pressure. Thecardiac, renal and vascular responses increase the workload of theheart, further accelerating myocardial damage and exacerbating the heartfailure state. Accordingly, it is desirable to reduce the level ofsympathetic nervous system activation in order to stop or at leastminimize this vicious cycle and thereby treat or manage the heartfailure.

A number of drug treatments have been proposed for the management ofhypertension, heart failure and other cardiovascular disorders. Theseinclude vasodilators to reduce the blood pressure and ease the workloadof the heart, diuretics to reduce fluid overload, inhibitors andblocking agents of the body's neurohormonal responses, and othermedicaments.

Various surgical procedures have also been proposed for these maladies.For example, heart transplantation has been proposed for patients whosuffer from severe, refractory heart failure. Alternatively, animplantable medical device such as a ventricular assist device (VAD) maybe implanted in the chest to increase the pumping action of the heart.Alternatively, an intra-aortic balloon pump (IABP) may be used formaintaining heart function for short periods of time, but typically nolonger than one month. Other surgical procedures are available as well.

It has been known for decades that the wall of the carotid sinus, astructure at the bifurcation of the common carotid arteries, containsstretch receptors (baroreceptors) that are sensitive to blood pressure.These receptors send signals via the carotid sinus nerve to the brain,which in turn regulates the cardiovascular system to maintain normalblood pressure (the baroreflex), in part through modulation of theautonomic nervous system. Electrical stimulation of the carotid sinusnerve (baropacing) has previously been proposed for therapeuticpurposes. For example, U.S. Pat. No. 6,073,048 to Kieval et al., thefull disclosure of which is incorporated herein by reference, disclosesa system and method for stimulating the carotid sinus nerve based onvarious cardiovascular and pulmonary parameters.

Although each of these alternative approaches is beneficial in someways, each of the therapies has its own disadvantages. For example, drugtherapy is often incompletely effective. Some patients may beunresponsive (refractory) to medical therapy. Drugs often have unwantedside effects and may need to be given in complex regimens. These andother factors contribute to poor patient compliance with medicaltherapy. Drug therapy may also be expensive, adding to the health carecosts associated with these disorders. Likewise, surgical approaches arevery costly, may be associated with significant patient morbidity andmortality and may not alter the natural history of the disease.Accordingly, there continues to be a substantial and long felt need fornew devices and methods for treating and/or managing high bloodpressure, heart failure and their associated cardiovascular and nervoussystem disorders.

U.S. Pat. No. 6,522,926, assigned to the assignee of the presentapplication and incorporated herein fully by reference, describes anumber of systems and methods intended to activate the baroreflexsystem, typically by providing activation at or near one or morebaroreceptors in the carotid sinus and elsewhere. Numerous specificapproaches are described, including the use of coil electrodes placedover the exterior of the carotid sinus near the carotid bifurcation.U.S. patent application Ser. No. 10/402,911, assigned to the assignee ofthe present application and incorporated herein fully by reference,describes improved systems and methods for baroreflex activation toprovide cardiovascular reflex control. U.S. patent application Ser. No.10/402,393, assigned to the assignee of the present application andincorporated herein fully by reference, describes improved systems andmethods for baroreflex activation for cardiovascular reflex control viacoupled electrodes.

Other devices, methods and systems for baroreflex activation aredescribed in U.S. patent application Ser. Nos. 09/702,089, 09/963,991,09/964,079, 09/963,777, 10/284,063, 10/453,678, 60/505,121 and60/513,642, all of which are assigned to the present assignee and all ofwhich are hereby incorporated by reference. Some of these devices andmethods, for example, use baroreflex activation for such purposes asepilepsy control (60/505,121) and pain control and sedation(60/513,642). In using these and other systems and methods foractivating baroreceptors and/or structures in the area of baroreceptorssuch as nerve fibers connected to baroreceptors, carotid sinus nervesand the like, an implantable stimulation/activation device is typicallyplaced in the patient. Currently available systems and methods, however,do not provide a way to test the efficacy of a baroreflex activationimplant before it is implanted. Current systems also do not provide away to determine where an implant should be placed in a patient, such aswhether a 2-sided or 1-sided device should be implanted in a givenpatient's neck, and if 1-sided, then on which side.

Devices and methods for externally stimulating baroreceptors to monitorand control a patient's blood pressure are described in U.S. Pat. Nos.6,050,952 and 5,727,558 to Hakki et al., the full disclosures of whichare incorporated fully herein by reference. These devices and methods,however, are designed only for therapeutic use and do not provide forexternal baroreflex activation to assess patient response, help aphysician choose a location in the patient's body for placing theimplant, or the like. Thus, currently available baroreflex activationtreatments generally involve attaching cumbersome external devices to apatient or implanting an implantable device without knowing beforehandwhether it will work for a given patient.

Therefore, a need exists for devices and methods for evaluating apatient response to baroreflex activation before implanting anactivation device in the patient. Ideally, such devices and methodswould be non-invasive, external to the patient, or as minimally invasiveas possible and would help determine whether a patient will have adesired response to an implantable baroreflex activation device. Alsoideally, such devices and methods would help a physician decide where toimplant a baroreflex activation device in a patient. It would also beideal if such devices could be used with or incorporated into otherimplantable devices, such as cardiac pacemakers (including biventricularpacemakers), cardiac defibrillators or the like. At least some of theseobjectives will be met by the present invention.

BRIEF SUMMARY OF THE INVENTION

The present invention provides a number of methods and systems forexternally applying a baroreflex stimulus to test or confirm abaroreflex in a patient. Such external stimulation allows a physician todecide how effective an implantable baroreflex activation device wouldbe in a given patient and/or in what location (or locations) to implantsuch a device. By providing a non-invasive screening technique of thistype, the methods and systems of the present invention help physiciansand patients avoid unnecessary surgical implantation of baroreflexactivation devices.

The present invention also provides for a number of devices, systems andmethods by which the blood pressure, nervous system activity, andneurohormonal activity may be selectively and controllably regulated byactivating the baroreflex system. These devices, systems and methods maybe implemented, for example, after a physician determines, via themethods and systems just described for external baroreflex activation,that baroreflex activation will provide a desired response in a givenpatient. By selectively and controllably activating a baroreflex, thepresent invention reduces excessive blood pressure, sympathetic nervoussystem activation and neurohormonal activation, thereby minimizing theirdeleterious effects on the heart, vasculature and other organs andtissues. For further description of devices, systems and methods forselectively and controllably activating a baroreflex reference may bemade to U.S. patent application Ser. Nos. 09/702,089, 09/963,991,09/964,079, 09/963,777, 10/284,063, 10/402,911, 10/402,393, 10/453,678,60/505,121 and 60/513,642, which were previously incorporated byreference.

In one aspect of the present invention, a method for testing response tobaroreflex activation in a patient involves applying at least a firstbaroreflex activation stimulus to the patient from a location externalto the patient, measuring at least one physiological parameter of thepatient, and determining, from the physiological parameter measurement,to what extent the baroreflex activation stimulus caused a baroreflexresponse in the patient. Generally, the externally applied baroreflexactivation stimulus may be any type, form or amount of stimulus. In someembodiments, for example, applying the baroreflex activation stimuluscomprises transmitting energy from at least one energy transmittingdevice, mechanically stimulating an area approximating one or morecarotid arteries, and/or introducing one or more drugs into the patient.

In many embodiments, the externally applied stimulus comprises some typeof transmitted energy. Examples of such transmitted energy include butare not limited to ultrasonic, electromagnetic, radiofrequency andmicrowave energy. In one embodiment, for example, electromagnetic energymay be transmitted to the patient using at least one electrode externalto the patient. In another embodiment, transmitted energy comprisestranscutaneous electrical nerve stimulation (TENS). Again, any energytype, form, amount, pattern or the like may be used.

In general, the one or more externally applied baroreflex activationstimuli may be directed toward stimulating a baroreflex via any suitableanatomical structure or structures. In other words, a stimulus maydirected at any of a number of various structures to cause baroreflexactivation. For example, stimulus may be directed toward one or morecarotid sinus nerves, toward one or more carotid baroreceptors, towardother baroreceptors located elsewhere in the body, toward baroreceptoror afferent nerve fibers located in one or more blood vessel walls,toward carotid sinus nerve fibers and/or the like. Thus, the presentinvention encompasses the application of any external stimulus toactivate a baroreflex and is not limited to stimulus of any specificanatomical structure or location. This activation is typically describedas “baroreflex activation.” Activation, according to the presentinvention, may occur directly at, near or in the vicinity of one or morebaroreceptors, but is not limited to direct baroreceptor activation. Forexample, as just mentioned, various nerve fibers may be activatedinstead of or in addition to baroreceptors.

Similarly, any suitable physiological parameter (or multiple parameters)may be measured according to various embodiments of the presentinvention, for determining whether the applied stimulus has causedbaroreflex activation. In various embodiments, for example, parameterswhich may be measured include but are not limited to blood pressure,change in blood pressure, heart rate, cardiac output, vascularresistance, seizure activity, neurological activity and/or painsensation. In some embodiments, determining whether baroreflexactivation has occurred involves comparing the one or more physiologicalparameter measurements to one or more baseline measurements. Such amethod may optionally involve taking the baseline measurement of thephysiological parameter of the patient before externally applying thebaroreflex stimulus. Alternatively, one or more threshold measurementlevels may be set, and a comparison of the physiological parametermeasurements to the threshold(s) may be used to determine whether abaroreflex occurred.

In one embodiment, a method of the invention includes determiningwhether to place an implantable baroreflex activation device in thepatient, based on whether the baroreflex activation stimulus caused abaroreflex. Such a method may further include determining one or morelocations in the patient's body in which to place the implantabledevice. In one embodiment, for example, determining the one or morelocations comprises determining whether to place the implantable devicein a left side and/or a right side of the patient's neck. Such methodsmay optionally further involve placing one or more implantablebaroreflex activation devices in the patient.

In some embodiments, the method further involves: applying a secondbaroreflex activation stimulus to the patient from the location externalto the patient, with the second stimulus having at least one differentcharacteristic than the first; measuring at least one physiologicalparameter of the patient; and determining, from the physiologicalparameter measurement, to what extent the second baroreflex activationstimulus caused a baroreflex response in the patient. Optionally, themethod may further include repeating the applying, measuring anddetermining steps multiple times, each time using a stimulus having atleast one different characteristic, and generating data describing theextent to which different baroreflex stimuli cause different baroreflexresponses. For example, different characteristics may include but arenot limited to intensity, pulse amplitude, pulse width and pulsefrequency. In some embodiments, the method then involves selecting onebaroreflex stimulus for treating the patient, based on the data. Alsooptionally, some embodiments involve applying baroreflex stimuli frommultiple different locations external to the patient and generating datato describe the extent to which baroreflex stimuli from the differentexternal locations cause different baroreflex responses. Such a methodmay further include selecting an intensity and a location for treatingthe patient based on the data.

In another aspect of the present invention, a system for testingresponse to baroreflex activation in a patient includes at least oneexternal baroreflex activation device for applying at least onebaroreflex activation stimulus to the patient from a location externalto the patient and at least one physiological parameter measuring devicefor measuring a physiological parameter of the patient to determine towhat extent the applied stimulus caused a baroreflex activation in thepatient. The external baroreflex activation device may be any suitabledevice, such as but not limited to an energy transmission device, amechanical force application device and a drug delivery device. When anenergy transmission device is used, it may be any suitable device,including but not limited to an ultrasonic, electromagnetic,radiofrequency and/or microwave energy device. In some embodiments, forexample, the energy transmission device comprises an ultrasonic energytransmission device for externally activating carotid sinusbaroreceptors, other baroreceptors, carotid sinus nerve fibers and/orother never fibers connected to baroreceptors. In another embodiment theenergy transmission device comprises at least one electrode forexternally activating carotid sinus baroreceptors, other baroreceptors,carotid sinus nerve fibers and/or other never fibers connected tobaroreceptors. Alternatively, the device may be a TENS unit forexternally activating carotid sinus baroreceptors, other baroreceptors,carotid sinus nerve fibers and/or other never fibers connected tobaroreceptors.

In some embodiments, the at least one physiological parameter measuringdevice comprises at least one surface electrode for contacting with thepatient's skin to measure the physiological parameter. Alternatively,the physiological parameter measuring device may comprise at least onepiezoelectric sensor for contacting with the patient's skin to measurethe physiological parameter. In other embodiments, the measuring devicemay comprise a blood pressure cuff, a pulse oximetry device, a Swan-Ganzcatheter a device for measuring cardiac output, a device for measuringvascular resistance, electroencephalogram device and/or the like. Anysuitable measuring device or combination of devices, either now known orhereafter discovered, may be used without departing from the scope ofthe present invention. Such devices may be used to measure any suitablephysiological parameter or parameters, such as but not limited to bloodpressure, change in blood pressure, heart rate, cardiac output, vascularresistance, seizure activity, neurological activity and/or painsensation.

In some embodiments, the system may also include a processor forreceiving physiological parameter measurements from the measuring deviceand processing the measurements into data in a usable form. For example,such a processor may compare measured physiological parameter data toone or more baseline measurement values to determine whether the appliedstimulus has caused baroreflex activation in the patient. In someembodiments, the system may further include a display monitor coupledwith the processor for displaying measured physiological parameter datato a user.

In some embodiments, the system additionally includes at least oneimplantable baroreflex activation device for placing in the patient.Such an implantable device may include any suitable device, such asthose described in further detail below, those described in U.S. patentapplication Ser. Nos. 09/702,089, 09/963,991, 09/964,079, 09/963,777,10/284,063, 10/402,911 and 10/402,393, 10/453,678, 60/505,121 and60/513,642 (previously incorporated by reference) or any other suitabledevice or combination of devices. In one embodiment, an implantablebaroreflex activation device may be coupled with another implantabledevice for performing another function in the patient. This otherimplantable device, for example, may include but is not limited to acardiac pacemaker, an implantable defibrillator, an implantablecardioverter defibrillator, a drug pump and/or a neurostimulator.

These and other aspects and embodiments of the present invention aredescribed in further detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of the upper torso of a human body,showing the major arteries and veins and associated anatomy.

FIG. 2A is a cross-sectional schematic illustration of the carotid sinusand baroreceptors within the vascular wall.

FIG. 2B is a schematic illustration of baroreceptors within the vascularwall and the baroreflex system.

FIG. 3 is a schematic illustration of the upper torso of a human body,demonstrating a system for externally applying a baroreflex activationstimulus to the body and measuring a physiological parameter.

FIG. 4 is a schematic illustration of a baroreflex activation system inaccordance with the present invention.

FIGS. 5A and 5B are schematic illustrations of a baroreflex activationdevice in the form of an implantable extraluminal conductive structurewhich electrically induces a baroreceptor signal in accordance with anembodiment of the present invention.

FIGS. 6A-6F are schematic illustrations of various possible arrangementsof electrodes around the carotid sinus for extravascular electricalactivation embodiments.

FIG. 7 is a schematic illustration of a serpentine shaped electrode forextravascular electrical activation embodiments.

FIG. 8 is a schematic illustration of a plurality of electrodes alignedorthogonal to the direction of wrapping around the carotid sinus forextravascular electrical activation embodiments.

FIGS. 9-12 are schematic illustrations of various multi-channelelectrodes for extravascular electrical activation embodiments.

FIG. 13 is a schematic illustration of an extravascular electricalactivation device including a tether and an anchor disposed about thecarotid sinus and common carotid artery.

FIG. 14 is a schematic illustration of an alternative extravascularelectrical activation device including a plurality of ribs and a spine.

FIG. 15 is a schematic illustration of an electrode assembly forextravascular electrical activation embodiments.

FIG. 16 is a schematic illustration of a fragment of an alternativecable for use with an electrode assembly such as shown in FIG. 15.

FIG. 17 illustrates a foil strain gauge for measuring expansion force ofa carotid artery or other blood vessel.

FIG. 18 illustrates a transducer which is adhesively connected to thewall of an artery.

FIG. 19 is a cross-sectional view of the transducer of FIG. 18.

FIG. 20 illustrates a first exemplary electrode assembly having anelastic base and plurality of attachment tabs.

FIG. 21 is a more detailed illustration of the electrode-carryingsurface of the electrode assembly of FIG. 20.

FIG. 22 is a detailed illustration of electrode coils which are presentin an elongate lead of the electrode assembly of FIG. 20.

FIG. 23 is a detailed view of the electrode-carrying surface of anelectrode assembly similar to that shown in FIG. 21, except that theelectrodes have been flattened.

FIG. 24 is a cross-sectional view of the electrode structure of FIG. 22.

FIG. 25 illustrates the transition between the flattened andnon-flattened regions of the electrode coil of the electrode assemblyFIG. 21.

FIG. 26 is a cross-sectional view taken along the line 26-26 of FIG. 25.

FIG. 27 is a cross-sectional view taken along the line 27-27 of FIG. 25.

FIG. 28 is an illustration of a further exemplary electrode assemblyconstructed in accordance with the principles of the present invention.

FIG. 29 illustrates the electrode assembly of FIG. 28 wrapped around thecommon carotid artery near the carotid bifurcation.

FIG. 30 illustrates the electrode assembly of FIG. 28 wrapped around theinternal carotid artery.

FIG. 31 is similar to FIG. 30, but with the carotid bifurcation having adifferent geometry.

DETAILED DESCRIPTION OF THE INVENTION

To better understand the present invention, it may be useful to explainsome of the basic vascular anatomy associated with the cardiovascularsystem. Referring to FIG. 1, a schematic illustration of the upper torsoof a human body 10 shows some of the major arteries and veins of thecardiovascular system. The left ventricle of the heart 11 pumpsoxygenated blood up into the aortic arch 12. The right subclavian artery13, the right common carotid artery 14, the left common carotid artery15 and the left subclavian artery 16 branch off the aortic arch 12proximal of the descending thoracic aorta 17. Although relatively short,a distinct vascular segment referred to as the brachiocephalic artery 22connects the right subclavian artery 13 and the right common carotidartery 14 to the aortic arch 12. The right carotid artery 14 bifurcatesinto the right external carotid artery 18 and the right internal carotidartery 19 at the right carotid sinus 20. Although not shown for purposesof clarity only, the left carotid artery 15 similarly bifurcates intothe left external carotid artery and the left internal carotid artery atthe left carotid sinus.

From the aortic arch 12, oxygenated blood flows into the carotidarteries 18/19 and the subclavian arteries 13/16. From the carotidarteries 18/19, oxygenated blood circulates through the head andcerebral vasculature and oxygen depleted blood returns to the heart 11by way of the jugular veins, of which only the right internal jugularvein 21 is shown for sake of clarity. From the subclavian arteries13/16, oxygenated blood circulates through the upper peripheralvasculature and oxygen depleted blood returns to the heart by way of thesubclavian veins, of which only the right subclavian vein 23 is shown,also for sake of clarity. The heart 11 pumps the oxygen depleted bloodthrough the pulmonary system where it is re-oxygenated. There-oxygenated blood returns to the heart 11 which pumps there-oxygenated blood into the aortic arch as described above, and thecycle repeats.

Within the arterial walls of the aortic arch 12, common carotid arteries14/15 (near the right carotid sinus 20 and left carotid sinus),subclavian arteries 13/16 and brachiocephalic artery 22 there arebaroreceptors 30. For example, as best seen in FIG. 2A, baroreceptors 30reside within the vascular walls of the carotid sinus 20. Baroreceptors30 are a type of stretch receptor used by the body to sense bloodpressure. In general, the term “baroreceptors” may refer tobaroreceptors themselves as well as other receptors that act likebaroreceptors. An increase in blood pressure causes the arterial wall tostretch, and a decrease in blood pressure causes the arterial wall toreturn to its original size. Such a cycle is repeated with each beat ofthe heart. Because baroreceptors 30 are located within the arterialwall, they are able to sense deformation of the adjacent tissue, whichis indicative of a change in blood pressure. The baroreceptors 30located in the right carotid sinus 20, the left carotid sinus and theaortic arch 12 may play the most significant role in sensing bloodpressure that affects the baroreflex system 50, which is described inmore detail with reference to FIG. 2B.

Refer now to FIG. 2B, which shows a schematic illustration ofbaroreceptors 30 disposed in a generic vascular wall 40 and a schematicflow chart of the baroreflex system 50. Baroreceptors 30 are profuselydistributed within the arterial walls 40 of the major arteries discussedpreviously, and generally form an arbor 32. The baroreceptor arbor 32comprises a plurality of baroreceptors 30, each of which transmitsbaroreceptor signals to the brain 52 via nerve 38. The baroreceptors 30are so profusely distributed and arborized within the vascular wall 40that discrete baroreceptor arbors 32 are not readily discernable. Tothis end, the baroreceptors 30 shown in FIG. 2B are primarily schematicfor purposes of illustration.

Baroreflex signals are used to activate a number of body systems whichcollectively may be referred to as the baroreflex system 50.Baroreceptors 30 (and other baroreceptor-like receptors) are connectedto the brain 52 via the nervous system 51. Thus, the brain 52 is able todetect changes in blood pressure, which is indicative of cardiac output.If cardiac output is insufficient to meet demand (i.e., the heart 11 isunable to pump sufficient blood), the baroreflex system 50 activates anumber of body systems, including the heart 11, kidneys 53, vessels 54,and other organs/tissues. Such activation of the baroreflex system 50generally corresponds to an increase in neurohormonal activity.Specifically, the baroreflex system 50 initiates a neurohormonalsequence that signals the heart 11 to increase heart rate and increasecontraction force in order to increase cardiac output, signals thekidneys 53 to increase blood volume by retaining sodium and water, andsignals the vessels 54 to constrict to elevate blood pressure. Thecardiac, renal and vascular responses increase blood pressure andcardiac output 55, and thus increase the workload of the heart 11.Conversely, if a patient's blood pressure is elevated, the oppositebaroreflex response typically occurs.

To address the problems of hypertension, heart failure, othercardiovascular disorders and renal disorders, the present inventionprovides a number of devices, systems and methods by which thebaroreflex system 50 is activated to reduce excessive blood pressure,autonomic nervous system activity and neurohormonal activation. Althoughmuch of the following description focuses on use of baroreflexactivation to treat cardiovascular conditions, however, the invention isin no way limited to such applications. In fact, according to variousembodiments, baroreceptor activation may be used for any other suitablepurpose, such as for controlling seizure activity to treat epilepsy(described fully in U.S. Patent Application Ser. No. 60/505,121) or forpain control and/or sedation (described fully in U.S. Patent ApplicationSer. No. 60/513,642). Other embodiments may involve baroreflexactivation for any other suitable purpose.

In particular, the present invention provides a number of devices,systems and methods by which baroreceptors 30 and other baroreflexstructures may be activated, thereby indicating an increase in bloodpressure and signaling the brain 52 to reduce the body's blood pressureand level of sympathetic nervous system and neurohormonal activation,and increase parasypathetic nervous system activation, thus having abeneficial effect on the cardiovascular system and other body systems.As was previously discussed, various embodiments of the presentinvention may operate by activating baroreceptors 30, other receptors,nerve fibers connected to one or more baroreceptors, such as carotidsinus nerve fibers, or any other suitable structure for causing abaroreflex, and activation may be provided directly at a structure or inthe vicinity of a structure. This type of activation is generallyreferred to herein as “baroreflex activation.” For convenience, thephrase “activating baroreceptors” may often be used to generally referto activating any of the structures just mentioned for causingbaroreflex activation.

With reference now to FIG. 3, the present invention generally provides asystem for externally applying a stimulus to a patient 130 to invoke abaroreflex and measuring one or more physiological parameters. Themeasured parameter(s) may then be used to determine to what extent theapplied stimulus caused a baroreflex, thus providing a physician withinformation as to the efficacy an implantable baroreflex activationdevice will have in a given patient. Generally, a baroreflexactivation/measuring system includes at least one baroreflex activationdevice 132 and at least one physiological parameter measuring device140. In various embodiments, activation device 132 may comprise, forexample, an energy transmission device, a mechanical force applicationdevice for applying massage to a carotid artery, a drug delivery devicefor delivering one or more drugs to patient 130 to elicit a baroreflexand/or the like. Any suitable device or combination of devices may beused. In FIG. 3, activation device 132 comprises an energyelectromagnetic energy source 133 coupled with two electrodes 136 viatwo leads 134. Alternatively, energy source 133 may comprise anultrasound energy source, microwave energy source, TENS unit, RF energysource or a source of any other suitable energy. Electrodes 136 mayalternatively comprise any other energy transmission members, such asultrasound transmission members or the like.

Although electrodes 136 are shown coupled with the patient's 130 neck,they could alternatively be placed at any other suitable location foractivating a baroreflex. For example, they could be coupled with thepatient near another location where baroreceptors or baroreceptor nervesare present. Alternatively, one or more energy transmission members maybe positioned so as to not contact the patient. Any number of energytransmission members may be used, with some embodiments including onlyone and other including multiple energy transmission units. And asmentioned, other modalities may be used for activating a baroreflex,such as mechanical stimulation, drug activation and/or the like.

Measuring device 140 may similarly include any suitable device orcombination of devices. In the embodiment shown, measuring device 140 isa sphygmomanometer, but any other suitable device may be used, such as apulse oximeter, a Swan-Ganz catheter, an ECG or EEG device, or the like.Any parameter indicative of a baroreflex may be measured, such as bloodpressure, change in blood pressure, heart rate, cardiac output, vascularresistance, seizure activity, neurological activity, pain sensation,patient sedation and/or the like. Using measuring device 140, aphysician may determine the extent to which a baroreflex has been causedby application of a stimulus by activation device 132, and thus maydetermine whether an implantable activation device will achieve adesired result. In some instances, a physician may decide thatbaroreflex activation is not desirable in a given patient and will thusdecide not to implant an activation device.

In some embodiments, multiple baroreflex stimuli may be applied to apatient and the resulting baroreflex activations after application ofthe stimuli can be compared. For example, stimuli of differentintensities and/or applied from different locations may be compared anddata describing the results of those stimuli may be provided to aphysician. The physician may then use the data to choose an optimal ordesirable location(s) for placing one or more implantable activatorsand/or to choose an intensity at which to set the activator(s). Tofacilitate such a process, in some embodiments a system may furtherinclude a processor for processing measurements taken by measuringdevice 140 and/or a monitor or other read-out mechanism for providinguseful data to a physician user.

Once a physician determines that a given patient will respond favorablyto an implanted baroreflex stimulation device, the next step may be toactually implant such a device. The following description focuses on anumber of implantable devices for baroreflex activation. However, theinvention is in no way limited to use of the implantable devicesdescribed below. In fact, any suitable implantable device may optionallybe used as part of a method or system of the present invention. In someembodiments, for example, an implantable device or system may alsoinclude one or more external components or parts, which are disposedoutside the patient's body during treatment.

That being said, and with reference now to FIG. 4, the present inventiongenerally provides a system including a control system 60, a baroreflexactivation device 70, and a sensor 80 (optional), which generallyoperate in the following manner. The sensor(s) 80 optionally sensesand/or monitors a parameter (e.g., cardiovascular function) indicativeof the need to modify the baroreflex system and generates a signalindicative of the parameter. The control system 60 generates a controlsignal as a function of the received sensor signal. The control signalactivates, deactivates or otherwise modulates the baroreflex activationdevice 70. Typically, activation of the device 70 results in activationof the baroreceptors 30 (or other baroreflex structures). Alternatively,deactivation or modulation of the baroreflex activation device 70 maycause or modify activation of the baroreceptors 30. The baroreflexactivation device 70 may comprise a wide variety of devices whichutilize electrical means to activate baroreceptors 30. Thus, when thesensor 80 detects a parameter indicative of the need to modify thebaroreflex system activity (e.g., excessive blood pressure), the controlsystem 60 generates a control signal to modulate (e.g. activate) thebaroreflex activation device 70 thereby inducing a baroreflex signalthat is perceived by the brain 52 to be apparent excessive bloodpressure. When the sensor 80 detects a parameter indicative of normalbody function (e.g., normal blood pressure), the control system 60generates a control signal to modulate (e.g., deactivate) the baroreflexactivation device 70.

As mentioned previously, the baroreflex activation device 70 maycomprise a wide variety of devices which utilize electrical means toactivate the baroreceptors 30. The baroreflex activation device 70 ofthe present invention comprises an electrode structure which directlyactivates one or more baroreceptors 30 by changing the electricalpotential across the baroreceptors 30. It is possible that changing theelectrical potential across the tissue surrounding the baroreceptors 30may cause the surrounding tissue to stretch or otherwise deform, thusmechanically activating the baroreceptors 30, in which case thestretchable and elastic electrode structures of the present inventionmay provide significant advantages.

All of the specific embodiments of the electrode structures of thepresent invention are suitable for implantation, and are preferablyimplanted using a minimally invasive surgical approach. The baroreflexactivation device 70 may be positioned anywhere baroreceptors 30 arepresent. Such potential implantation sites are numerous, such as theaortic arch 12, in the common carotid arteries 18/19 near the carotidsinus 20, in the subclavian arteries 13/16, in the brachiocephalicartery 22, or in other arterial or venous locations. The electrodestructures of the present invention will be implanted such that they arepositioned on or over a vascular structure at or near the baroreceptors30. Preferably, the electrode structure of the baroreflex activationdevice 70 is implanted near the right carotid sinus 20 and/or the leftcarotid sinus (near the bifurcation of the common carotid artery) and/orthe aortic arch 12, where baroreceptors 30 have a significant impact onthe baroreflex system 50. For purposes of illustration only, the presentinvention is described with reference to baroreflex activation device 70positioned near the carotid sinus 20.

The optional sensor 80 is operably coupled to the control system 60 byelectric sensor cable or lead 82. The sensor 80 may comprise anysuitable device that measures or monitors a parameter indicative of theneed to modify the activity of the baroreflex system. For example, thesensor 80 may comprise a physiologic transducer or gauge that measuresECG, blood pressure (systolic, diastolic, average or pulse pressure),blood volumetric flow rate, blood flow velocity, blood pH, O2 or CO2content, mixed venous oxygen saturation (SVO2), vasoactivity, nerveactivity, tissue activity, body movement, activity levels, respiration,or composition. Examples of suitable transducers or gauges for thesensor 80 include ECG electrodes, a piezoelectric pressure transducer,an ultrasonic flow velocity transducer, an ultrasonic volumetric flowrate transducer, a thermodilution flow velocity transducer, a capacitivepressure transducer, a membrane pH electrode, an optical detector(SVO2), tissue impedance (electrical), or a strain gauge. Although onlyone sensor 80 is shown, multiple sensors 80 of the same or differenttype at the same or different locations may be utilized.

An example of an implantable blood pressure measurement device that maybe disposed about a blood vessel is disclosed in U.S. Pat. No. 6,106,477to Miesel et al., the entire disclosure of which is incorporated hereinby reference. An example of a subcutaneous ECG monitor is available fromMedtronic under the trade name REVEAL ILR and is disclosed in PCTPublication No. WO 98/02209, the entire disclosure of which isincorporated herein by reference. Other examples are disclosed in U.S.Pat. Nos. 5,987,352 and 5,331,966, the entire disclosures of which areincorporated herein by reference. Examples of devices and methods formeasuring absolute blood pressure utilizing an ambient pressurereference are disclosed in U.S. Pat. No. 5,810,735 to Halperin et al.,U.S. Pat. No. 5,904,708 to Goedeke, and PCT Publication No. WO 00/16686to Brockway et al., the entire disclosures of which are incorporatedherein by reference. The sensor 80 described herein may take the form ofany of these devices or other devices that generally serve the samepurpose.

The sensor 80 may be positioned in/on a major artery such as the aorticarch 12, a common carotid artery 14/15, a subclavian artery 13/16 or thebrachiocephalic artery 22, or in a chamber of the heart 11, such thatthe parameter of interest may be readily ascertained. The sensor 80 maybe disposed inside the body such as in or on an artery, a vein or anerve (e.g. vagus nerve), or disposed outside the body, depending on thetype of transducer or gauge utilized. The sensor 80 may be separate fromthe baroreflex activation device 70 or combined therewith. For purposesof illustration only, the sensor 80 is shown positioned on the rightsubclavian artery 13.

By way of example, the control system 60 includes a control block 61comprising a processor 63 and a memory 62. Control system 60 isconnected to the sensor 80 by way of sensor cable 82. Control system 60is also connected to the baroreflex activation device 70 by way ofelectric control cable 72. Thus, the control system 60 receives a sensorsignal from the sensor 80 by way of sensor cable 82, and transmits acontrol signal to the baroreflex activation device 70 by way of controlcable 72.

The system components 60/70/80 may be directly linked via cables 72/82or by indirect means such as RF signal transceivers, ultrasonictransceivers or galvanic couplings. Examples of such indirectinterconnection devices are disclosed in U.S. Pat. No. 4,987,897 toFunke and U.S. Pat. No. 5,113,859 to Funke, the entire disclosures ofwhich are incorporated herein by reference.

The memory 62 may contain data related to the sensor signal, the controlsignal, and/or values and commands provided by the input device 64. Thememory 62 may also include software containing one or more algorithmsdefining one or more functions or relationships between the controlsignal and the sensor signal. The algorithm may dictate activation ordeactivation control signals depending on the sensor signal or amathematical derivative thereof. The algorithm may dictate an activationor deactivation control signal when the sensor signal falls below alower predetermined threshold value, rises above an upper predeterminedthreshold value or when the sensor signal indicates a specificphysiologic event. The algorithm may dynamically alter the thresholdvalue as determined by the sensor input values.

As mentioned previously, the baroreflex activation device 70 activatesbaroreceptors 30 and/or other baroreflex structures electrically,optionally in combination with mechanical, thermal, chemical, biologicalor other co-activation. In some instances, the control system 60includes a driver 66 to provide the desired power mode for thebaroreflex activation device 70. For example, the driver 66 may comprisea power amplifier or the like and the cable 72 may comprise electricallead(s). In other instances, the driver 66 may not be necessary,particularly if the processor 63 generates a sufficiently strongelectrical signal for low level electrical actuation of the baroreflexactivation device 70.

The control system 60 may operate as a closed loop utilizing feedbackfrom the sensor 80, or other sensors, such as heart rate sensors whichmay be incorporated or the electrode assembly, or as an open looputilizing reprogramming commands received by input device 64. The closedloop operation of the control system 60 preferably utilizes somefeedback from the transducer 80, but may also operate in an open loopmode without feedback. Programming commands received by the input device64 may directly influence the control signal, the output activationparameters, or may alter the software and related algorithms containedin memory 62. The treating physician and/or patient may provide commandsto input device 64. Display 65 may be used to view the sensor signal,control signal and/or the software/data contained in memory 62.

The control signal generated by the control system 60 may be continuous,periodic, alternating, episodic or a combination thereof, as dictated byan algorithm contained in memory 62. Continuous control signals includea constant pulse, a constant train of pulses, a triggered pulse and atriggered train of pulses. Examples of periodic control signals includeeach of the continuous control signals described above which have adesignated start time (e.g., beginning of each period as designated byminutes, hours, or days in combinations of) and a designated duration(e.g., seconds, minutes, hours, or days in combinations of). Examples ofalternating control signals include each of the continuous controlsignals as described above which alternate between the right and leftoutput channels. Examples of episodic control signals include each ofthe continuous control signals described above which are triggered by anepisode (e.g., activation by the physician/patient, an increase/decreasein blood pressure above a certain threshold, heart rate above/belowcertain levels, etc.).

The stimulus regimen governed by the control system 60 may be selectedto promote long term efficacy. It is theorized that uninterrupted orotherwise unchanging activation of the baroreceptors 30 may result inthe baroreceptors and/or the baroreflex system becoming less responsiveover time, thereby diminishing the long term effectiveness of thetherapy. Therefore, the stimulus regimen maybe selected to activate,deactivate or otherwise modulate the baroreflex activation device 70 insuch a way that therapeutic efficacy is maintained preferably for years.

In addition to maintaining therapeutic efficacy over time, the stimulusregimens of the present invention may be selected reduce powerrequirement/consumption of the system 60. As will be described in moredetail hereinafter, the stimulus regimen may dictate that the baroreflexactivation device 70 be initially activated at a relatively higherenergy and/or power level, and subsequently activated at a relativelylower energy and/or power level. The first level attains the desiredinitial therapeutic effect, and the second (lower) level sustains thedesired therapeutic effect long term. By reducing the energy and/orpower levels after the desired therapeutic effect is initially attained,the energy required or consumed by the activation device 70 is alsoreduced long term. This may correlate into systems having greaterlongevity and/or reduced size (due to reductions in the size of thepower supply and associated components).

A first general approach for a stimulus regimen which promotes long termefficacy and reduces power requirements/consumption involves generatinga control signal to cause the baroreflex activation device 70 to have afirst output level of relatively higher energy and/or power, andsubsequently changing the control signal to cause the baroreflexactivation device 70 to have a second output level of relatively lowerenergy and/or power. The first output level may be selected andmaintained for sufficient time to attain the desired initial effect(e.g., reduced heart rate and/or blood pressure), after which the outputlevel may be reduced to the second level for sufficient time to sustainthe desired effect for the desired period of time.

For example, if the first output level has a power and/or energy valueof X1, the second output level may have a power and/or energy value ofX2, wherein X2 is less than X1. In some instances, X2 may be equal tozero, such that the first level is “on” and the second level is “off”.It is recognized that power and energy refer to two differentparameters, and in some cases, a change in one of the parameters (poweror energy) may not correlate to the same or similar change in the otherparameter. In the present invention, it is contemplated that a change inone or both of the parameters may be suitable to obtain the desiredresult of promoting long term efficacy.

It is also contemplated that more than two levels may be used. Eachfurther level may increase the output energy or power to attain thedesired effect, or decrease the output energy or power to retain thedesired effect. For example, in some instances, it may be desirable tohave further reductions in the output level if the desired effect may besustained at lower power or energy levels. In other instances,particularly when the desired effect is diminishing or is otherwise notsustained, it may be desirable to increase the output level until thedesired effect is reestablished, and subsequently decrease the outputlevel to sustain the effect.

The transition from each level may be a step function (e.g., a singlestep or a series of steps), a gradual transition over a period of time,or a combination thereof. In addition, the signal levels may becontinuous, periodic, alternating, or episodic as discussed previously.

In electrical activation using a non modulated signal, the output (poweror energy) level of the baroreflex activation device 70 may be changedby adjusting the output signal voltage level, current level and/orsignal duration. The output signal of the baroreflex activation device70 may be, for example, constant current or constant voltage. Inelectrical activation embodiments using a modulated signal, wherein theoutput signal comprises, for example, a series of pulses, several pulsecharacteristics may be changed individually or in combination to changethe power or energy level of the output signal. Such pulsecharacteristics include, but are not limited to: pulse amplitude (PA),pulse frequency (PF), pulse width or duration (PW), pulse waveform(square, triangular, sinusoidal, etc.), pulse polarity (for bipolarelectrodes) and pulse phase (monophasic, biphasic).

In electrical activation wherein the output signal comprises a pulsetrain, several other signal characteristics may be changed in additionto the pulse characteristics described above, as described in copendingapplication Ser. No. 09/964,079, the full disclosure of which isincorporated herein by reference.

FIGS. 5A and 5B show schematic illustrations of a baroreflex activationdevice 300 in the form of an extravascular electrically conductivestructure or electrode 302. The electrode structure 302 may comprise acoil, braid or other structure capable of surrounding the vascular wall.Alternatively, the electrode structure 302 may comprise one or moreelectrode patches distributed around the outside surface of the vascularwall. Because the electrode structure 302 is disposed on the outsidesurface of the vascular wall, intravascular delivery techniques may notbe practical, but minimally invasive surgical techniques will suffice.The extravascular electrode structure 302 may receive electrical signalsdirectly from the driver 66 of the control system 60 by way ofelectrical lead 304, or indirectly by utilizing an inductor (not shown)as described in commonly assigned application Ser. No. 10/402,393,previously incorporated by reference.

Refer now to FIGS. 6A-6F which show schematic illustrations of variouspossible arrangements of electrodes around the carotid sinus 20 forextravascular electrical activation embodiments, such as baroreflexactivation device 300 described with reference to FIGS. 4A and 4B. Theelectrode designs illustrated and described hereinafter may beparticularly suitable for connection to the carotid arteries at or nearthe carotid sinus, and may be designed to minimize extraneous tissuestimulation.

In FIGS. 6A-6F, the carotid arteries are shown, including the common 14,the external 18 and the internal 19 carotid arteries. The location ofthe carotid sinus 20 may be identified by a landmark bulge 21, which istypically located on the internal carotid artery 19 just distal of thebifurcation, or extends across the bifurcation from the common carotidartery 14 to the internal carotid artery 19.

The carotid sinus 20, and in particular the bulge 21 of the carotidsinus, may contain a relatively high density of baroreceptors 30 (notshown) in the vascular wall. For this reason, it may be desirable toposition the electrodes 302 of the activation device 300 on and/oraround the sinus bulge 21 to maximize baroreceptor responsiveness and tominimize extraneous tissue stimulation.

It should be understood that the device 300 and electrodes 302 aremerely schematic, and only a portion of which may be shown, for purposesof illustrating various positions of the electrodes 302 on and/or aroundthe carotid sinus 20 and the sinus bulge 21. In each of the embodimentsdescribed herein, the electrodes 302 may be monopolar, bipolar, ortripolar (anode-cathode-anode or cathode-anode-cathode sets). Specificextravascular electrode designs are described in more detailhereinafter.

In FIG. 6A, the electrodes 302 of the extravascular electricalactivation device 300 extend around a portion or the entirecircumference of the sinus 20 in a circular fashion. Often, it would bedesirable to reverse the illustrated electrode configuration in actualuse. In FIG. 6B, the electrodes 302 of the extravascular electricalactivation device 300 extend around a portion or the entirecircumference of the sinus 20 in a helical fashion. In the helicalarrangement shown in FIG. 6B, the electrodes 302 may wrap around thesinus 20 any number of times to establish the desired electrode 302contact and coverage. In the circular arrangement shown in FIG. 6A, asingle pair of electrodes 302 may wrap around the sinus 20, or aplurality of electrode pairs 302 may be wrapped around the sinus 20 asshown in FIG. 6C to establish more electrode 302 contact and coverage.

The plurality of electrode pairs 302 may extend from a point proximal ofthe sinus 20 or bulge 21, to a point distal of the sinus 20 or bulge 21to ensure activation of baroreceptors 30 throughout the sinus 20 region.The electrodes 302 may be connected to a single channel or multiplechannels as discussed in more detail hereinafter. The plurality ofelectrode pairs 302 may be selectively activated for purposes oftargeting a specific area of the sinus 20 to increase baroreceptorresponsiveness, or for purposes of reducing the exposure of tissue areasto activation to maintain baroreceptor responsiveness long term.

In FIG. 6D, the electrodes 302 extend around the entire circumference ofthe sinus 20 in a criss-cross fashion. The criss-cross arrangement ofthe electrodes 302 establishes contact with both the internal 19 andexternal 18 carotid arteries around the carotid sinus 20. Similarly, inFIG. 6E, the electrodes 302 extend around all or a portion of thecircumference of the sinus 20, including the internal 19 and external 18carotid arteries at the bifurcation, and in some instances the commoncarotid artery 14. In FIG. 6F, the electrodes 302 extend around all or aportion of the circumference of the sinus 20, including the internal 19and external 18 carotid arteries distal of the bifurcation. In FIGS. 6Eand 6F, the extravascular electrical activation devices 300 are shown toinclude a substrate or base structure 306 which may encapsulate andinsulate the electrodes 302 and may provide a means for attachment tothe sinus 20 as described in more detail hereinafter.

From the foregoing discussion with reference to FIGS. 6A-6F, it shouldbe apparent that there are a number of suitable arrangements for theelectrodes 302 of the activation device 300, relative to the carotidsinus 20 and associated anatomy. In each of the examples given above,the electrodes 302 are wrapped around a portion of the carotidstructure, which may require deformation of the electrodes 302 fromtheir relaxed geometry (e.g., straight). To reduce or eliminate suchdeformation, the electrodes 302 and/or the base structure 306 may have arelaxed geometry that substantially conforms to the shape of the carotidanatomy at the point of attachment. In other words, the electrodes 302and the base structure or backing 306 may be pre shaped to conform tothe carotid anatomy in a substantially relaxed state. Alternatively, theelectrodes 302 may have a geometry and/or orientation that reduces theamount of electrode 302 strain. Optionally, as described in more detailbelow, the backing or base structure 306 may be elastic or stretchableto facilitate wrapping of and conforming to the carotid sinus or othervascular structure.

For example, in FIG. 7, the electrodes 302 are shown to have aserpentine or wavy shape. The serpentine shape of the electrodes 302reduces the amount of strain seen by the electrode material when wrappedaround a carotid structure. In addition, the serpentine shape of theelectrodes increases the contact surface area of the electrode 302 withthe carotid tissue. As an alternative, the electrodes 302 may bearranged to be substantially orthogonal to the wrap direction (i.e.,substantially parallel to the axis of the carotid arteries) as shown inFIG. 8. In this alternative, the electrodes 302 each have a length and awidth or diameter, wherein the length is substantially greater than thewidth or diameter. The electrodes 302 each have a longitudinal axisparallel to the length thereof, wherein the longitudinal axis isorthogonal to the wrap direction and substantially parallel to thelongitudinal axis of the carotid artery about which the device 300 iswrapped. As with the multiple electrode embodiments describedpreviously, the electrodes 302 may be connected to a single channel ormultiple channels as discussed in more detail hereinafter.

Refer now to FIGS. 9-12 which schematically illustrate variousmulti-channel electrodes for the extravascular electrical activationdevice 300. FIG. 8 illustrates a six (6) channel electrode assemblyincluding six (6) separate elongate electrodes 302 extending adjacent toand parallel with each other. The electrodes 302 are each connected tomulti-channel cable 304. Some of the electrodes 302 may be common,thereby reducing the number of conductors necessary in the cable 304.

Base structure or substrate 306 may comprise a flexible and electricallyinsulating material suitable for implantation, such as silicone, perhapsreinforced with a flexible material such as polyester fabric. The base306 may have a length suitable to wrap around all (360°) or a portion(i.e., less than 360°) of the circumference of one or more of thecarotid arteries adjacent the carotid sinus 20. The electrodes 302 mayextend around a portion (i.e., less than 360° such as 270°, 180° or 90°)of the circumference of one or more of the carotid arteries adjacent thecarotid sinus 20. To this end, the electrodes 302 may have a length thatis less than (e.g., 75%, 50% or 25%) the length of the base 206. Theelectrodes 302 may be parallel, orthogonal or oblique to the length ofthe base 306, which is generally orthogonal to the axis of the carotidartery to which it is disposed about. Preferably, the base structure orbacking will be elastic (i.e., stretchable), typically being composed ofat least in part of silicone, latex, or other elastomer. If such elasticstructures are reinforced, the reinforcement should be arranged so thatit does not interfere with the ability of the base to stretch andconform to the vascular surface.

The electrodes 302 may comprise round wire, rectangular ribbon or foilformed of an electrically conductive and radiopaque material such asplatinum. The base structure 306 substantially encapsulates theelectrodes 302, leaving only an exposed area for electrical connectionto extravascular carotid sinus tissue. For example, each electrode 302may be partially recessed in the base 206 and may have one side exposedalong all or a portion of its length for electrical connection tocarotid tissue. Electrical paths through the carotid tissues may bedefined by one or more pairs of the elongate electrodes 302.

In all embodiments described with reference to FIGS. 9-12, themulti-channel electrodes 302 may be selectively activated for purposesof mapping and targeting a specific area of the carotid sinus 20 todetermine the best combination of electrodes 302 (e.g., individual pair,or groups of pairs) to activate for maximum baroreceptor responsiveness,as described elsewhere herein. In addition, the multi-channel electrodes302 may be selectively activated for purposes of reducing the exposureof tissue areas to activation to maintain long term efficacy asdescribed, as described elsewhere herein. For these purposes, it may beuseful to utilize more than two (2) electrode channels. Alternatively,the electrodes 302 may be connected to a single channel whereby abaroreflex is uniformly activated throughout the sinus 20 region.

An alternative multi-channel electrode design is illustrated in FIG. 10.In this embodiment, the device 300 includes sixteen (16) individualelectrode pads 302 connected to 16 channel cable 304 via 4 channelconnectors 303. In this embodiment, the circular electrode pads 302 arepartially encapsulated by the base structure 306 to leave one face ofeach button electrode 302 exposed for electrical connection to carotidtissues. With this arrangement, electrical paths through the carotidtissues may be defined by one or more pairs (bipolar) or groups(tripolar) of electrode pads 302.

A variation of the multi-channel pad type electrode design isillustrated in FIG. 10. In this embodiment, the device 300 includessixteen (16) individual circular pad electrodes 302 surrounded bysixteen (16) rings 305, which collectively may be referred to asconcentric electrode pads 302/305. Pad electrodes 302 are connected to17 channel cable 304 via 4 channel connectors 303, and rings 305 arecommonly connected to 17 channel cable 304 via a single channelconnector 307. In this embodiment, the circular shaped electrodes 302and the rings 305 are partially encapsulated by the base structure 306to leave one face of each pad electrode 302 and one side of each ring305 exposed for electrical connection to carotid tissues. As analternative, two rings 305 may surround each electrode 302, with therings 305 being commonly connected. With these arrangements, electricalpaths through the carotid tissues may be defined between one or more padelectrode 302/ring 305 sets to create localized electrical paths.

Another variation of the multi-channel pad electrode design isillustrated in FIG. 12. In this embodiment, the device 300 includes acontrol IC chip 310 connected to 3 channel cable 304. The control chip310 is also connected to sixteen (16) individual pad electrodes 302 via4 channel connectors 303. The control chip 310 permits the number ofchannels in cable 304 to be reduced by utilizing a coding system. Thecontrol system 60 sends a coded control signal which is received by chip310. The chip 310 converts the code and enables or disables selectedelectrode 302 pairs in accordance with the code.

For example, the control signal may comprise a pulse wave form, whereineach pulse includes a different code. The code for each pulse causes thechip 310 to enable one or more pairs of electrodes, and to disable theremaining electrodes. Thus, the pulse is only transmitted to the enabledelectrode pair(s) corresponding to the code sent with that pulse. Eachsubsequent pulse would have a different code than the preceding pulse,such that the chip 310 enables and disables a different set ofelectrodes 302 corresponding to the different code. Thus, virtually anynumber of electrode pairs may be selectively activated using controlchip 310, without the need for a separate channel in cable 304 for eachelectrode 302. By reducing the number of channels in cable 304, the sizeand cost thereof may be reduced.

Optionally, the IC chip 310 may be connected to feedback sensor 80,taking advantage of the same functions as described with reference toFIG. 4. In addition, one or more of the electrodes 302 may be used asfeedback sensors when not enabled for activation. For example, such afeedback sensor electrode may be used to measure or monitor electricalconduction in the vascular wall to provide data analogous to an ECG.Alternatively, such a feedback sensor electrode may be used to sense achange in impedance due to changes in blood volume during a pulsepressure to provide data indicative of heart rate, blood pressure, orother physiologic parameter.

Refer now to FIG. 13 which schematically illustrates an extravascularelectrical activation device 300 including a support collar or anchor312. In this embodiment, the activation device 300 is wrapped around theinternal carotid artery 19 at the carotid sinus 20, and the supportcollar 312 is wrapped around the common carotid artery 14. Theactivation device 300 is connected to the support collar 312 by cables304, which act as a loose tether. With this arrangement, the collar 312isolates the activation device from movements and forces transmitted bythe cables 304 proximal of the support collar, such as may beencountered by movement of the control system 60 and/or driver 66. As analternative to support collar 312, a strain relief (not shown) may beconnected to the base structure 306 of the activation device 300 at thejuncture between the cables 304 and the base 306. With either approach,the position of the device 300 relative to the carotid anatomy may bebetter maintained despite movements of other parts of the system.

In this embodiment, the base structure 306 of the activation device 300may comprise molded tube, a tubular extrusion, or a sheet of materialwrapped into a tube shape utilizing a suture flap 308 with sutures 309as shown. The base structure 306 may be formed of a flexible andbiocompatible material such as silicone, which may be reinforced with aflexible material such as polyester fabric available under the tradename DACRON® to form a composite structure. The inside diameter of thebase structure 306 may correspond to the outside diameter of the carotidartery at the location of implantation, for example 6 to 8 mm. The wallthickness of the base structure 306 may be very thin to maintainflexibility and a low profile, for example less than 1 mm. If the device300 is to be disposed about a sinus bulge 21, a correspondingly shapedbulge may be formed into the base structure for added support andassistance in positioning.

The electrodes 302 (shown in phantom) may comprise round wire,rectangular ribbon or foil, formed of an electrically conductive andradiopaque material such as platinum or platinum iridium. The electrodesmay be molded into the base structure 306 or adhesively connected to theinside diameter thereof, leaving a portion of the electrode exposed forelectrical connection to carotid tissues. The electrodes 302 mayencompass less than the entire inside circumference (e.g., 300°) of thebase structure 306 to avoid shorting. The electrodes 302 may have any ofthe shapes and arrangements described previously. For example, as shownin FIG. 13, two rectangular ribbon electrodes 302 may be used, eachhaving a width of 1 mm spaced 1.5 mm apart.

The support collar 312 may be formed similarly to base structure 306.For example, the support collar may comprise molded tube, a tubularextrusion, or a sheet of material wrapped into a tube shape utilizing asuture flap 315 with sutures 313 as shown. The support collar 312 may beformed of a flexible and biocompatible material such as silicone, whichmay be reinforced to form a composite structure. The cables 304 aresecured to the support collar 312, leaving slack in the cables 304between the support collar 312 and the activation device 300.

In all embodiments described herein, it may be desirable to secure theactivation device to the vascular wall using sutures or other fixationmeans. For example, sutures 311 may be used to maintain the position ofthe electrical activation device 300 relative to the carotid anatomy (orother vascular site containing baroreceptors, nerve fibers or the like).Such sutures 311 may be connected to base structure 306, and passthrough all or a portion of the vascular wall. For example, the sutures311 may be threaded through the base structure 306, through theadventitia of the vascular wall, and tied. If the base structure 306comprises a patch or otherwise partially surrounds the carotid anatomy,the corners and/or ends of the base structure may be sutured, withadditional sutures evenly distributed therebetween. In order to minimizethe propagation of a hole or a tear through the base structure 306, areinforcement material such as polyester fabric may be embedded in thesilicone material. In addition to sutures, other fixation means may beemployed such as staples or a biocompatible adhesive, for example.

Refer now to FIG. 14 which schematically illustrates an alternativeextravascular electrical activation device 300 including one or moreelectrode ribs 316 interconnected by spine 317. Optionally, a supportcollar 312 having one or more (non electrode) ribs 316 may be used toisolate the activation device 300 from movements and forces transmittedby the cables 304 proximal of the support collar 312.

The ribs 316 of the activation device 300 are sized to fit about thecarotid anatomy, such as the internal carotid artery 19 adjacent thecarotid sinus 20. Similarly, the ribs 316 of the support collar 312 maybe sized to fit about the carotid anatomy, such as the common carotidartery 14 proximal of the carotid sinus 20. The ribs 316 may beseparated, placed on a carotid artery, and closed thereabout to securethe device 300 to the carotid anatomy.

Each of the ribs 316 of the device 300 includes an electrode 302 on theinside surface thereof for electrical connection to carotid tissues. Theribs 316 provide insulating material around the electrodes 302, leavingonly an inside portion exposed to the vascular wall. The electrodes 302are coupled to the multi-channel cable 304 through spine 317. Spine 317also acts as a tether to ribs 316 of the support collar 312, which donot include electrodes since their function is to provide support. Themulti-channel electrode 302 functions discussed with reference to FIGS.9-12 are equally applicable to this embodiment.

The ends of the ribs 316 may be connected (e.g., sutured) after beingdisposed about a carotid artery, or may remain open as shown. If theends remain open, the ribs 316 may be formed of a relatively stiffmaterial to ensure a mechanical lock around the carotid artery. Forexample, the ribs 316 may be formed of polyethylene, polypropylene,PTFE, or other similar insulating and biocompatible material.Alternatively, the ribs 316 may be formed of a metal such as stainlesssteel or a nickel titanium alloy, as long as the metallic material waselectrically isolated from the electrodes 302. As a further alternative,the ribs 316 may comprise an insulating and biocompatible polymericmaterial with the structural integrity provided by metallic (e.g.,stainless steel, nickel titanium alloy, etc.) reinforcement. In thislatter alternative, the electrodes 302 may comprise the metallicreinforcement.

Refer now to FIG. 15 which schematically illustrates a specific exampleof an electrode assembly for an extravascular electrical activationdevice 300. In this specific example, the base structure 306 comprises asilicone sheet having a length of 5.0 inches, a thickness of 0.007inches, and a width of 0.312 inches. The electrodes 302 compriseplatinum ribbon having a length of 0.47 inches, a thickness of 0.0005inches, and a width of 0.040 inches. The electrodes 302 are adhesivelyconnected to one side of the silicone sheet 306.

The electrodes 302 are connected to a modified bipolar endocardialpacing lead, available under the trade name CONIFIX from Innomedica (nowBIOMEC Cardiovascular, Inc.), model number 501112. The proximal end ofthe cable 304 is connected to the control system 60 or driver 66 asdescribed previously. The pacing lead is modified by removing the pacingelectrode to form the cable body 304. The MP35 wires are extracted fromthe distal end thereof to form two coils 318 positioned side by sidehaving a diameter of about 0.020 inches. The coils 318 are then attachedto the electrodes utilizing 316 type stainless steel crimp terminalslaser welded to one end of the platinum electrodes 302. The distal endof the cable 304 and the connection between the coils 318 and the endsof the electrodes 302 are encapsulated by silicone.

The cable 304 illustrated in FIG. 15 comprises a coaxial type cableincluding two coaxially disposed coil leads separated into two separatecoils 318 for attachment to the electrodes 302. An alternative cable 304construction is illustrated in FIG. 16. FIG. 16 illustrates analternative cable body 304 which may be formed in a curvilinear shapesuch as a sinusoidal configuration, prior to implantation. Thecurvilinear configuration readily accommodates a change in distancebetween the device 300 and the control system 60 or the driver 66. Sucha change in distance may be encountered during flexion and/or extensionof the neck of the patient after implantation.

In this alternative embodiment, the cable body 304 may comprise two ormore conductive wires 304 a arranged coaxially or collinearly as shown.Each conductive wire 304 a may comprise a multifilament structure ofsuitable conductive material such as stainless steel or MP35N. Aninsulating material may surround the wire conductors 304 a individuallyand/or collectively. For purposes of illustration only, a pair ofelectrically conductive wires 304 a having an insulating materialsurrounding each wire 304 a individually is shown. The insulated wires304 a may be connected by a spacer 304 b comprising, for example, aninsulating material. An additional jacket of suitable insulatingmaterial may surround each of the conductors 304 a. The insulatingjacket may be formed to have the same curvilinear shape of the insulatedwires 304 a to help maintain the shape of the cable body 304 duringimplantation.

If a sinusoidal configuration is chosen for the curvilinear shape, theamplitude (A) may range from 1 mm to 10 mm, and preferably ranges from 2mm to 3 mm. The wavelength (WL) of the sinusoid may range from 2 mm to20 mm, and preferably ranges from 4 mm to 10 mm. The curvilinear orsinusoidal shape may be formed by a heat setting procedure utilizing afixture which holds the cable 304 in the desired shape while the cableis exposed to heat. Sufficient heat is used to heat set the conductivewires 304 a and/or the surrounding insulating material. After cooling,the cable 304 may be removed from the fixture, and the cable 304 retainsthe desired shape.

Refer now to FIGS. 17-19 which illustrate various transducers that maybe mounted to the wall of a vessel such as a carotid artery 14 tomonitor wall expansion or contraction using strain, force and/orpressure gauges. An example of an implantable blood pressure measurementdevice that may be disposed about a blood vessel is disclosed in U.S.Pat. No. 6,106,477 to Miesel et al., the entire disclosure of which isincorporated herein by reference. The output from such gauges may becorrelated to blood pressure and/or heart rate, for example, and may beused to provide feedback to the control system 60 as describedpreviously herein. In FIG. 17, an implantable pressure measuringassembly comprises a foil strain gauge or force sensing resistor device740 disposed about an artery such as common carotid artery 14. Atransducer portion 742 may be mounted to a silicone base or backing 744which is wrapped around and sutured or otherwise attached to the artery14.

Alternatively, the transducer 750 may be adhesively connected to thewall of the artery 14 using a biologically compatible adhesive such ascyanoacrylate as shown in FIG. 18. In this embodiment, the transducer750 comprises a micro machined sensor (MEMS) that measures force orpressure. The MEMS transducer 750 includes a micro arm 752 (shown insection in FIG. 19) coupled to a silicon force sensor contained over anelastic base 754. A cap 756 covers the arm 752 a top portion of the base754. The base 754 include an interior opening creating access from thevessel wall 14 to the arm 752. An incompressible gel 756 fills the spacebetween the arm 752 and the vessel wall 14 such that force istransmitted to the arm upon expansion and contraction of the vesselwall. In both cases, changes in blood pressure within the artery causechanges in vessel wall stress which are detected by the transducer andwhich may be correlated with the blood pressure.

Refer now to FIGS. 20-22 which illustrate an alternative extravascularelectrical activation device 700, which, may also be referred to as anelectrode cuff device or more generally as an “electrode assembly.”Except as described herein and shown in the drawings, device 700 may bethe same in design and function as extravascular electrical activationdevice 300 described previously.

As seen in FIGS. 20 and 21, electrode assembly or cuff device 700includes coiled electrode conductors 702/704 embedded in a flexiblesupport 706. In the embodiment shown, an outer electrode coil 702 and aninner electrode coil 704 are used to provide a pseudo tripolararrangement, but other polar arrangements are applicable as well asdescribed previously. The coiled electrodes 702/704 may be formed offine round, flat or ellipsoidal wire such as 0.002 inch diameter roundPtIr alloy wire wound into a coil form having a nominal diameter of0.015 inches with a pitch of 0.004 inches, for example. The flexiblesupport or base 706 may be formed of a biocompatible and flexible(preferably elastic) material such as silicone or other suitable thinwalled elastomeric material having a wall thickness of 0.005 inches anda length (e.g., 2.95 inches) sufficient to surround the carotid sinus,for example.

Each turn of the coil in the contact area of the electrodes 702/704 isexposed from the flexible support 706 and any adhesive to form aconductive path to the artery wall. The exposed electrodes 702/704 mayhave a length (e.g., 0.236 inches) sufficient to extend around at leasta portion of the carotid sinus, for example. The electrode cuff 700 isassembled flat with the contact surfaces of the coil electrodes 702/704tangent to the inside plane of the flexible support 706. When theelectrode cuff 700 is wrapped around the artery, the inside contactsurfaces of the coiled electrodes 702/704 are naturally forced to extendslightly above the adjacent surface of the flexible support, therebyimproving contact to the artery wall.

The ratio of the diameter of the coiled electrodes 702/704 to the wirediameter is preferably large enough to allow the coil to bend andelongate without significant bending stress or torsional stress in thewire. Flexibility is a significant advantage of this design which allowsthe electrode cuff 700 to conform to the shape of the carotid artery andsinus, and permits expansion and contraction of the artery or sinuswithout encountering significant stress or fatigue. In particular, theflexible electrode cuff 700 may be wrapped around and stretched toconform to the shape of the carotid sinus and artery duringimplantation. This may be achieved without collapsing or distorting theshape of the artery and carotid sinus due to the compliance of theelectrode cuff 700. The flexible support 706 is able to flex and stretchwith the conductor coils 702/704 because of the absence of fabricreinforcement in the electrode contact portion of the cuff 700. Byconforming to the artery shape, and by the edge of the flexible support706 sealing against the artery wall, the amount of stray electricalfield and extraneous stimulation will likely be reduced.

The pitch of the coil electrodes 702/704 may be greater than the wirediameter in order to provide a space between each turn of the wire tothereby permit bending without necessarily requiring axial elongationthereof. For example, the pitch of the contact coils 702/704 may be0.004 inches per turn with a 0.002 inch diameter wire, which allows fora 0.002 inch space between the wires in each turn. The inside of thecoil may be filled with a flexible adhesive material such as siliconeadhesive which may fill the spaces between adjacent wire turns. Byfilling the small spaces between the adjacent coil turns, the chance ofpinching tissue between coil turns is minimized thereby avoidingabrasion to the artery wall. Thus, the embedded coil electrodes 702/704are mechanically captured and chemically bonded into the flexiblesupport 706. In the unlikely event that a coil electrode 702/704 comesloose from the support 706, the diameter of the coil is large enough tobe atraumatic to the artery wall. Preferably, the centerline of the coilelectrodes 702/704 lie near the neutral axis of electrode cuff structure700 and the flexible support 706 comprises a material with isotropicelasticity such as silicone in order to minimize the shear forces on theadhesive bonds between the coil electrodes 702/704 and the support 706.

The electrode coils 702/704 are connected to corresponding conductivecoils 712/714, respectively, in an elongate lead 710 which is connectedto the control system 60. Anchoring wings 718 may be provided on thelead 710 to tether the lead 710 to adjacent tissue and minimize theeffects or relative movement between the lead 710 and the electrode cuff700. As seen in FIG. 22, the conductive coils 712/714 may be formed of0.003 MP35N bifilar wires wound into 0.018 inch diameter coils which areelectrically connected to electrode coils 702/704 by splice wires 716.The conductive coils 712/714 may be individually covered by aninsulating covering 718 such as silicone tubing and collectively coveredby insulating covering 720.

The conductive material of the electrodes 702/704 may be a metal asdescribed above or a conductive polymer such as a silicone materialfilled with metallic particles such as Pt particles. In this latterembodiment, the polymeric electrodes may be integrally formed with theflexible support 706 with the electrode contacts comprising raised areason the inside surface of the flexible support 706 electrically coupledto the lead 710 by wires or wire coils. The use of polymeric electrodesmay be applied to other electrode design embodiments described elsewhereherein.

Reinforcement patches 708 such as DACRON® fabric may be selectivelyincorporated into the flexible support 706. For example, reinforcementpatches 708 may be incorporated into the ends or other areas of theflexible support 706 to accommodate suture anchors. The reinforcementpatches 708 provide points where the electrode cuff 700 may be suturedto the vessel wall and may also provide tissue in growth to furtheranchor the device 700 to the exterior of the vessel wall. For example,the fabric reinforcement patches 708 may extend beyond the edge of theflexible support 706 so that tissue in growth may help anchor theelectrode assembly or cuff 700 to the vessel wall and may reducereliance on the sutures to retain the electrode assembly 700 in place.As a substitute for or in addition to the sutures and tissue in growth,bioadhesives such as cyanoacrylate may be employed to secure the device700 to the vessel wall. In addition, an adhesive incorporatingconductive particles such as Pt coated micro spheres may be applied tothe exposed inside surfaces of the electrodes 702/704 to enhanceelectrical conduction to the tissue and possibly limit conduction alongone axis to limit extraneous tissue stimulation.

The reinforcement patches 708 may also be incorporated into the flexiblesupport 706 for strain relief purposes and to help retain the coils702/704 to the support 706 where the leads 710 attach to the electrodeassembly 700 as well as where the outer coil 702 loops back around theinner coil 704. Preferably, the patches 708 are selectively incorporatedinto the flexible support 706 to permit expansion and contraction of thedevice 700, particularly in the area of the electrodes 702/704. Inparticular, the flexible support 706 is only fabric reinforced inselected areas thereby maintaining the ability of the electrode cuff 700to stretch.

Referring now to FIGS. 23-27, the electrode assembly of FIGS. 20-22 canbe modified to have “flattened” coil electrodes in the region of theassembly where the electrodes contact the extravascular tissue. As shownin FIG. 23, an electrode-carrying surface 801 of the electrode assembly,is located generally between parallel reinforcement strips or tabs 808.The flattened coil section 810 will generally be exposed on a lowersurface 803 of the base 806 (FIG. 24) and will be covered orencapsulated by a parylene or other polymeric structure or material 802over an upper surface 805 thereof. The coil is formed with a generallycircular periphery 809, as best seen in FIGS. 25 and 27, and may bemechanically flattened, typically over a silicone or other supportinginsert 815, as best seen in FIG. 26. The use of the flattened coilstructure is particularly beneficial since it retains flexibility,allowing the electrodes to bend, stretch, and flex together with theelastomeric base 806, while also increasing the flat electrode areaavailable to contact the extravascular surface.

Referring now to FIGS. 28-31, an additional electrode assembly 900constructed in accordance with the principles of the present inventionwill be described. Electrode assembly 900 comprises an electrode base,typically an elastic base 902, typically formed from silicone or otherelastomeric material, having an electrode-carrying surface 904 and aplurality of attachment tabs 906 (906 a, 906 b, 906 c, and 906 d)extending from the electrode-carrying surface. The attachment tabs 906are preferably formed from the same material as the electrode-carryingsurface 904 of the base 902, but could be formed from other elastomericmaterials as well. In the latter case, the base will be molded,stretched or otherwise assembled from the various pieces. In theillustrated embodiment, the attachment tabs 906 are formed integrallywith the remainder of the base 902, i.e., typically being cut from asingle sheet of the elastomeric material.

The geometry of the electrode assembly 900, and in particular thegeometry of the base 902, is selected to permit a number of differentattachment modes to the blood vessel. In particular, the geometry of theassembly 902 of FIG. 28 is intended to permit attachment to variouslocations on the carotid arteries at or near the carotid sinus andcarotid bifurcation.

A number of reinforcement regions 910 (910 a, 910 b, 910 c, 910 d, and910 e) are attached to different locations on the base 902 to permitsuturing, clipping, stapling, or other fastening of the attachment tabs906 to each other and/or the electrode-carrying surface 904 of the base902. In the preferred embodiment intended for attachment at or aroundthe carotid sinus, a first reinforcement strip 910 a is provided over anend of the base 902 opposite to the end which carries the attachmenttabs. Pairs of reinforcement strips 910 b and 910 c are provided on eachof the axially aligned attachment tabs 906 a and 906 b, while similarpairs of reinforcement strips 910 d and 910 e are provided on each ofthe transversely angled attachment tabs 906 c and 906 d. In theillustrated embodiment, all attachment tabs will be provided on one sideof the base, preferably emanating from adjacent corners of therectangular electrode-carrying surface 904.

The structure of electrode assembly 900 permits the surgeon to implantthe electrode assembly so that the electrodes 920 (which are preferablystretchable, flat-coil electrodes as described in detail above), arelocated at a preferred location relative to the target baroreceptors.The preferred location may be determined, for example, as described incopending application Ser. No. 09/963,991, filed on Sep. 26, 2001, thefull disclosure of which incorporated herein by reference.

Once the preferred location for the electrodes 920 of the electrodeassembly 900 is determined, the surgeon may position the base 902 sothat the electrodes 920 are located appropriately relative to theunderlying baroreceptors. Thus, the electrodes 920 may be positionedover the common carotid artery CC as shown in FIG. 29, or over theinternal carotid artery IC, as shown in FIGS. 30 and 31. In FIG. 29, theassembly 900 may be attached by stretching the base 902 and attachmenttabs 906 a and 906 b over the exterior of the common carotid artery. Thereinforcement tabs 906 a or 906 b may then be secured to thereinforcement strip 910 a, either by suturing, stapling, fastening,gluing, welding, or other well-known means. Usually, the reinforcementtabs 906 c and 906 d will be cut off at their bases, as shown at 922 and924, respectively.

In other cases, the bulge of the carotid sinus and the baroreceptors maybe located differently with respect to the carotid bifurcation. Forexample, as shown in FIG. 30, the receptors may be located further upthe internal carotid artery IC so that the placement of electrodeassembly 900 as shown in FIG. 29 will not work. The assembly 900,however, may still be successfully attached by utilizing thetransversely angled attachment tabs 906 c and 906 d rather than thecentral or axial tabs 906 a and 906 b. As shown in FIG. 30, the lowertab 906 d is wrapped around the common carotid artery CC, while theupper attachment tab 906 c is wrapped around the internal carotid arteryIC. The axial attachment tabs 906 a and 906 b will usually be cut off(at locations 926), although neither of them could in some instancesalso be wrapped around the internal carotid artery IC. Again, the tabswhich are used may be stretched and attached to reinforcement strip 910a, as generally described above.

Referring to FIG. 31, in instances where the carotid bifurcation hasless of an angle, the assembly 900 may be attached using the upper axialattachment tab 906 a and be lower transversely angled attachment tab 906d. Attachment tabs 906 b and 906 c may be cut off, as shown at locations928 and 930, respectively. In all instances, the elastic nature of thebase 902 and the stretchable nature of the electrodes 920 permit thedesired conformance and secure mounting of the electrode assembly overthe carotid sinus. It would be appreciated that these or similarstructures would also be useful for mounting electrode structures atother locations in the vascular system.

In most activation device embodiments described herein, it may bedesirable to incorporate anti-inflammatory agents (e.g., steroid elutingelectrodes) such as described in U.S. Pat. No. 4,711,251 to Stokes, U.S.Pat. No. 5,522,874 to Gates and U.S. Pat. No. 4,972,848 to Di Domenicoet al., the entire disclosures of which are incorporated herein byreference. Such agents reduce tissue inflammation at the chronicinterface between the device (e.g., electrodes) and the vascular walltissue, to thereby increase the efficiency of stimulus transfer, reducepower consumption, and maintain activation efficiency, for example.

Any of the devices described above may be used alone or with othercompatible devices. In some embodiments, in fact, an implantable devicefor baroreceptor activation may be incorporated with another implantabledevice for performing a related or entirely different function. Forexample, it may be advantageous to incorporate a baroreflex activationdevice as described above with an implantable cardiac pacemaker such asa bi-ventricular pacing device, defibrillator, cardioverterdefibrillator, a drug pump, a neurostimulator and/or the like. Thus, itis contemplated within the scope of the invention that various devicesfor providing baroreflex activation may be suitable for use with orincorporation into any other suitable implantable device.

The present invention may be manifested in a variety of forms other thanthe specific embodiments described and contemplated herein. Accordingly,departures in form and detail may be made without departing from thescope and spirit of the present invention as described in the appendedclaims.

1. A method for testing response to baroreflex activation in a patient,the method comprising: applying at least a first baroreflex activationstimulus to the patient from a location external to the patient;measuring at least one physiological parameter of the patient;determining, from the physiological parameter measurement, to whatextent the first baroreflex activation stimulus caused a baroreflexresponse in the patient; and determining whether to place an implantablebaroreflex activation device in the patient based on the extent to whichthe baroreflex activation stimulus caused the baroreflex response.
 2. Amethod as in claim 1, wherein applying the baroreflex activationstimulus comprises at least one of transmitting energy from at least oneenergy transmitting device, mechanically stimulating an areaapproximating one or more carotid arteries, and introducing one or moredrugs into the patient.
 3. A method as in claim 2, wherein thetransmitted energy comprises at least one of ultrasonic,electromagnetic, radiofrequency and microwave energy.
 4. A method as inclaim 3, wherein the transmitted energy comprises electromagnetic energyusing at least one electrode external to the patient.
 5. A method as inclaim 2, wherein the transmitted energy comprises transcutaneouselectrical nerve stimulation.
 6. A method as in claim 1, wherein thefirst baroreflex activation stimulus is applied so as to activate atleast one carotid sinus baroreceptor.
 7. A method as in claim 1, whereinthe first baroreflex activation stimulus is applied so as to activate atleast one baroreceptor other than a carotid sinus baroreceptor.
 8. Amethod as in claim 1, wherein the first baroreflex activation stimulusis applied so as to activate at least one carotid sinus nerve fiber. 9.A method as in claim 1, wherein the first baroreflex activation stimulusis applied so as to activate at least one nerve fiber other than acarotid sinus nerve fiber.
 10. A method as in claim 1, wherein measuringthe physiological parameter comprises measuring at least one of bloodpressure, change in blood pressure, heart rate, cardiac output, vascularresistance, seizure activity, neurological activity and pain sensation.11. A method as in claim 1, wherein determining comprises comparing thephysiological parameter measurement to a baseline measurement.
 12. Amethod as in claim 11, further comprising measuring the baselinemeasurement of the physiological parameter of the patient beforeapplying the baroreflex activation stimulus.
 13. A method as in claim 1,wherein determining comprises comparing the physiological parametermeasurement to a predetermined threshold measurement.
 14. A method as inclaim 1, further comprising determining one or more locations in thepatient's body in which to place the implantable device.
 15. A method asin claim 14, wherein determining the one or more locations comprisesdetermining whether to place the implantable device in a left sideand/or a right side of the patient's neck.
 16. A method as in claim 1,further comprising placing at least one implantable baroreflexactivation device in the patient.
 17. A method as in claim 16, whereinat least part of the baroreflex activation device is placed external tothe patient's body.
 18. A method as in claim 1, further comprising:applying a second baroreflex activation stimulus to the patient from thelocation external to the patient, the second stimulus having at leastone different characteristic than the first stimulus; measuring at leastone physiological parameter of the patient; and determining, from thephysiological parameter measurement, to what extent the secondbaroreflex activation stimulus caused a baroreflex response in thepatient.
 19. A method as in claim 18, further comprising: repeating theapplying, measuring and determining steps multiple times, each timeapplying a baroreflex activation stimulus having at least one differentcharacteristic; and generating data describing the extent to whichdifferent baroreflex stimuli cause different baroreflex responses.
 20. Amethod as in claim 19, wherein the at least one different characteristiccomprises at least one of intensity, pulse amplitude, pulse width andpulse frequency.
 21. A method as in claim 19, further comprisingselecting one baroreflex stimulus for treating the patient, based on thedata.
 22. A method as in claim 19, further comprising applying at leastsome of the baroreflex stimuli from different locations external thepatient than other baroreflex stimuli, wherein the generated datafurther describe the extent to which baroreflex stimuli from differentexternal locations cause different baroreflex responses.
 23. A method asin claim 22, further comprising selecting one baroreflex stimulus andone location for applying the baroreflex stimulus for treating thepatient, based on the data.
 24. A system for testing response tobaroreflex activation in a patient, the system comprising: at least oneexternal baroreflex activation device for applying at least onebaroreflex activation stimulus to the patient from a location externalto the patient; and at least one physiological parameter measuringdevice for measuring a physiological parameter of the patient todetermine to what extent the applied stimulus caused a baroreflexactivation in the patient; and at least one implantable baroreflexactivation device for placing in the patient.
 25. A system as in claim24, wherein the at least one external baroreflex activation device isselected from the group consisting of an energy transmission device, amechanical force application device and a drug delivery device.
 26. Asystem as in claim 25, wherein the energy transmission device isselected from the group consisting of an ultrasonic, electromagnetic,radiofrequency and microwave energy device.
 27. A system as in claim 26,wherein the energy transmission device comprises an ultrasonic energytransmission device for externally activating at least one of carotidsinus baroreceptors, other baroreceptors, carotid sinus nerve fibers,nerve fibers connected to one or more baroreceptors, and other nervefibers.
 28. A system as in claim 26, wherein the energy transmissiondevice comprises at least one electrode for externally activating atleast one of carotid sinus baroreceptors, other baroreceptors, carotidsinus nerve fibers, nerve fibers connected to one or more baroreceptors,and other nerve fibers.
 29. A system as in claim 26, wherein the energytransmission device comprises at least one transcutaneous electricalnerve stimulator device for externally activating at least one ofcarotid sinus baroreceptors, other baroreceptors, carotid sinus nervefibers, nerve fibers connected to one or more baroreceptors, and othernerve fibers.
 30. A system as in claim 24, wherein the at least onephysiological parameter measuring device comprises at least one surfaceelectrode for contacting with the patient's skin to measure thephysiological parameter.
 31. A system as in claim 24, wherein the atleast one physiological parameter measuring device comprises at leastone piezoelectric sensor for contacting with the patient's skin tomeasure the physiological parameter.
 32. A system as in claim 24,wherein the at least one physiological parameter measuring device isselected from the group consisting of a blood pressure cuff, a pulseoximetry device, a Swan-Ganz catheter, a device for measuring cardiacoutput, a device for measuring vascular resistance and anelectroencephalogram device.
 33. A system as in claim 24, wherein the atleast one physiological parameter measuring device measures at least oneof blood pressure, change in blood pressure, heart rate, cardiac output,vascular resistance, seizure activity, neurological activity and painsensation.
 34. A system as in claim 24, further comprising a processorfor receiving physiological parameter measurements from the measuringdevice and processing the measurements into data in a usable form.
 35. Asystem as in claim 34, wherein the processor compares the measuredphysiological parameter data to one or more baseline measurement valuesto determine whether the applied stimulus has caused baroreflexactivation in the patient.
 36. A system as in claim 35, furthercomprising a display monitor coupled with the processor for displayingmeasured physiological parameter data to a user.
 37. A system as inclaim 24, wherein the implantable baroreflex activation device iscoupled with another implantable device for performing another functionin the patient.
 38. A system as in claim 37, wherein the otherimplantable device is selected from the group consisting of a cardiacpacemaker, an implantable defibrillator, an implantable cardioverterdefibrillator, a drug pump and a neurostimulator.
 39. A system as inclaim 24, wherein at least part of the implantable baroreflex activationdevice is disposed external to the patient's body.
 40. A method fortesting response to baroreflex activation in a patient, the methodcomprising: applying at least a first baroreflex activation stimulus tothe patient from a location external to the patient; measuring at leastone physiological parameter of the patient to provide a first measuredphysiological parameter; determining from the first measuredphysiological parameter measurement to what extent the first baroreflexactivation stimulus caused a baroreflex response in the patient;applying a second baroreflex activation stimulus to the patient from thelocation external to the patient, the second stimulus having at leastone different characteristic than the first stimulus; measuring at leastone physiological parameter of the patient to provide a second measuredphysiological parameter; determining from the second measuredphysiological parameter measurement, to what extent the secondbaroreflex activation stimulus caused a baroreflex response in thepatient; repeating the applying, measuring and determining stepsmultiple times, each time applying a baroreflex activation stimulushaving at least one different characteristic; generating data describingthe extent to which different baroreflex stimuli cause differentbaroreflex responses; and applying at least some of the baroreflexstimuli from different locations external the patient than otherbaroreflex stimuli, wherein the generated data further describe theextent to which baroreflex stimuli from different external locationscause different baroreflex responses.
 41. A method as in claim 40,wherein applying the baroreflex activation stimulis comprises at leastone of transmitting energy from at least one energy transmitting device,mechanically stimulating an area approximating one or more carotidarteries, and introducing one or more drugs into the patient.
 42. Amethod as in claim 41, wherein the transmitted energy comprises at leastone of ultrasonic, electromagnetic, radiofrequency and microwave energy.43. A method as in claim 42, wherein the transmitted energy compriseselectromagnetic energy using at least one electrode external to thepatient.
 44. A method as in claim 42, wherein the transmitted energycomprises transcutaneous electrical nerve stimulation.
 45. A method asin claim 40, wherein the first baroreflex activation stimulus is appliedso as to activate at least one carotid sinus baroreceptor.
 46. A methodas in claim 40, wherein the first baroreflex activation stimulus isapplied so as to activate at least one baroreceptor other than a carotidsinus baroreceptor.
 47. A method as in claim 40, wherein the firstbaroreflex activation stimulus is applied so as to activate at least onecarotid sinus nerve fiber.
 48. A method as in claim 40, wherein thefirst baroreflex activation stimulus is applied so as to activate atleast one nerve fiber other than a carotid sinus nerve fiber.
 49. Amethod as in claim 40, wherein measuring the physiological parameterscomprises measuring at least one of blood pressure, change in bloodpressure, heart rate, cardiac output, vascular resistance, seizureactivity, neurological activity and pain sensation.
 50. A method as inclaim 40, wherein determining comprises comparing the physiologicalparameter measurement to a baseline measurement.
 51. A method as inclaim 50, further comprising measuring the baseline measurement of thephysiological parameter of the patient before applying the baroreflexactivation stimulus.
 52. A method as in claim 40, wherein determiningcomprises comparing the physiological parameter measurement to apredetermined threshold measurement.
 53. A method as in claim 40,further comprising determining whether to place an implantablebaroreflex activation device in the patient, based on the extent towhich the baroreflex activation stimulus caused the baroreflex response.54. A method as in claim 53, further comprising determining one or morelocations in the patient's body in which to place the implantabledevice.
 55. A method as in claim 54, wherein determining the one or morelocations comprises determining whether to place the implantable devicein a left side and/or a right side of the patient's neck.
 56. A methodas in claim 53, further comprising placing at least one implantablebaroreflex activation device in the patient.
 57. A method as in claim56, wherein at least part of the baroreflex activation device is placedexternal to the patient's body.
 58. A method as in claim 40, wherein theat least one different characteristic comprises at least one ofintensity, pulse amplitude, pulse width and pulse frequency.
 59. Amethod as in claim 40, further comprising selecting one baroreflexstimulus for treating the patient, based on the data.
 60. A method as inclaim 40, further comprising selecting one baroreflex stimulus and onelocation for applying the baroreflex stimulus for treating the patient,based on the data.